Rodent Models of Type 2 Diabetes Mellitus

Hebron University Research Journal-A (Natural Sciences) - ((‫مجلة‬
‫ أ )العلوم الطبيعيه‬-‫جامعة الخليل للبحوث‬
Volume 7 Issue 1 Article 3
2017
Rodent Models of Type 2 Diabetes Mellitus

‫زكي طبيشه‬
‫جامعة الخليل‬, zakit@hebron.edu
Follow this and additional works at: https://digitalcommons.aaru.edu.jo/hujr_a
Part of the Life Sciences Commons
Recommended Citation
2017) ‫ زكي‬,‫" )طبيشه‬Rodent Models of Type 2 Diabetes Mellitus," Hebron University Research Journal-A
(Natural Sciences) - (‫ أ )العلوم الطبيعيه‬-‫مجلة جامعة الخليل للبحوث‬: Vol. 7 : Iss. 1 , Article 3.
Available at: https://digitalcommons.aaru.edu.jo/hujr_a/vol7/iss1/3
This Article is brought to you for free and open access by Arab Journals Platform. It has been accepted for
inclusion in Hebron University Research Journal-A (Natural Sciences) - (‫ أ )العلوم الطبيعيه‬-‫مجلة جامعة الخليل للبحوث‬
by an authorized editor. The journal is hosted on Digital Commons, an Elsevier platform. For more information,
please contact rakan@aaru.edu.jo, marah@aaru.edu.jo, dr_ahmad@aaru.edu.jo.
?????: Rodent Models of Type 2 Diabetes Mellitus
Hebron University Research Journal( A) H.U.R.J. is available online at

Vol.(7), pp.(32-14), 2017 http://www.hebron.edu/journal
Rodent Models of Type 2 Diabetes Mellitus
Dr. Zaki Ali Tubesha

Faculty of Agriculture
Hebron University
Abstract:
Diabetes is a disease characterized by a relative or absolute lack of insulin,
leading to hyperglycemia. Due to the high prevalence of diabetic
individuals all over the globe, extensive research is being carried out
effective to develop more antidiabetic agents and to determine their
mechanisms of action. Consequently, a number of diabetic animal models
have been developed and improved over the years, of which rodent models
are the most thoroughly described. The animal models of type 2 diabetes
can be obtained either spontaneously (genetics) or induced by chemicals,
dietary, surgical manipulations or by various combinations. In this review
my attention has been focused on gathering the animal models of type 2
diabetes, with reference to their characteristic, mechanisms, advantages
and disadvantages to the investigators in type 2 diabetes research. For
better and conclusive results, more than one animal model should be used
to represent the diversity seen in human diabetic patients.
Keywords: Animal models, Diabetes, Rodents, Obesity
:‫الملخص‬
.‫يتميّز مرض السكري بنقص األنسولين بكميات كبيرة أو جزئيّة تؤدي الرتفاع السكر في الدم‬
‫ تجرى اآلن الكثير من األبحاث إلنتاج و تطوير‬،ً‫بسبب االنتشار الواسع لداء السكري عالميا‬
‫ لذلك تم تطوير العديد من حيوانات التجارب‬.‫عالجات جديدة و دراسة آليّة عمل هذة األدوية‬
‫ حيث كانت القوارض من أكثر‬،‫كنموذج لمرض السكري و تم تحسينُها خالل السنوات الماضية‬
Published by Arab Journals Platform, 2017 1

ron University Research Journal-A (Natural Sciences) - (???? ????? ?????? ??????- ? (?????? ????????, Vol. 7 [2017], Iss. 1, A
Zaki Tubesha, Rodent Models of Type 2 Diabetes Mellitus, H.U.R.J, Vol. (7), 2017 33
‫ و يمكن تطوير حيوانات التجارب المصابة بالسكري من النوع الثاني إما‬،ً‫هذة الحيوانات استعماال‬
‫ أو الجمع بين الطُرق‬،ً ‫بشكل تلقائي (جينيّاً) أو من خالل استحداثها كيميائيّا ً وغذائيّا ً وجراحيّا‬
‫ هذا و تُبيِّنُ ال ُمراجعة ال ِعلميّة الحالية خصائص حيوانات التجارب المصابة بالسكري من‬.‫المذكورة‬
‫ باإلضافة إلبراز حسنات كل منها وسيئاتها كنموذج للباحثين في‬،‫ وكيفية استحداثها‬،‫النوع الثاني‬
‫ لِدراسة داء السكري من النوع الثاني على اإلنسان ال بُ َّد من‬.‫مجال السكري من النوع الثاني‬
‫استخدام أكثر من نموذج من حيوانات التجارب ليكون مماثالً ومشابها ً لهذا الداء عند المرضى من‬
.‫النوع الثاني‬
‫ السمنة‬،‫ القوارض‬،‫ السكري‬، ‫ نماذج حيوانات التجارب‬:‫الكلمات المفتاحية‬
Introduction
Diabetes of all types can lead to complications in various organs of the
body and can increase the risk of dying prematurely (Zone and Guide,
2017). Globally, an estimated 422 million adults were living with diabetes
in 2014, compared to 108 million in 1980 (WHO, 2016). To address the
urgent and challenging needs for better treatment options to control or
even eradicate diabetes mellitus, animal models closely resembling
disease characteristics are rapidly required to predict the efficacy and
safety of tested compounds in humans (Renner et al., 2016). Theoretically,
any organism can be used as a laboratory model for scientific
investigation, but only a few species are chosen to serve in biomedical
fields (Wall and Shani, 2008). However, to be defined as a laboratory
animal, the species must be bred and raised under certain conditions and
kept in a rigorously controlled environment under constant monitoring, so
that all microbiologic and genetic factors are known (Andersen and Tufik,
2015). Currently, rodents represent the dominant species in biomedical
research for their low cost, high reproductive potential, short life span,
adaptability to varied environments and sociability (Angelis et al., 2015).
In fact, 90% of laboratory animals are mice and rats, inclusion of guinea
pigs and rabbits brings this figure to 99%, while, the remaining 1% is
composed of dogs, cats, and non-human primates, among others
(Balcombe, 2006). Most diabetic patients, that is, 90% to 95%, suffer from
type 2 diabetes mellitus (T2DM), which is characterized by a combination
of insulin resistance and insulin secretion defects, with variable
manifestations resulting in relative insulin deficiency (Renner et al., 2016).
https://digitalcommons.aaru.edu.jo/hujr_a/vol7/iss1/3 2
In addition, medications used for the treatment of T2DM are associated

with problems of improper efficacy and negative side effects. So, there is a
continuous ongoing research for improved medications for diabetes and
insulin resistance (Tiwari, 2015). However, for an animal model to have
relevance to the study of diabetes, either the characteristics of the animal
model should reflect the pathophysiology or natural history of diabetes or
the model should develop complications of diabetes with an etiology
similar to that of the human condition (Cefalu, 2006). There appears to be
no single animal model that encompasses these entire characteristic; but
there are many models that provide very similar characteristics in one or
more aspects of T2DM in humans. The use of the appropriate animal
model based on these similarities, can provide much needed data on
pathophysiological mechanisms operative in human T2DM. Hence, this
review intends to give a detailed overview of the currently available
T2DM rodent’s animal models to be used in testing various classes of new
chemical brands.
Spontaneous (genetic) T2DM rodent models

Obese Models
Models of obesity with T2DM include two categories, monogenic (those
containing a mutation in the leptin or leptin receptor gene) and polygenic
models (Kanasaki and Koya, 2011). Obese rodents, such as ob/ob mice,
which is deficient in leptin and the db/db mice and Zucker Diabetic Fatty
rat, which are deficient in the leptin receptor, were used as monogenic
models. Obesity in these models is caused by leptin signaling deficiency
(King, 2012). Polygenic models may provide a more accurate model of the
human condition which includes KK mice, New Zealand Obese (NZO)
mice, TallyHo/Jng mice, and Otsuka Long Evans Tokushima Fatty
(OLETF) rat (Leiter, 2009).
Monogenic Models
Monogenic diabetes constitutes a heterogeneous group of single gene
disorders (Hattersley, 2005). The molecular background and clinical
picture of many of these diseases have been described (Fajans et al., 2001;
Hattersley, 1998; Malecki et al., 2008; McCarthy and Hattersley, 2001).
These models are divided into two major groups, resulting from impaired

insulin secretion or from an abnormal response to insulin (Klupa et al.,

2012).
ob/ob mice: The ob/obmice strain, from the Bar Harbor-Jackson

laboratory, has a well-known feature of leptin deficiency because of the
mutation identified in leptin gene leading to severe insulin resistance
(Oakes et al., 2005). In the early 1970s, these ob/ob mice were used to
investigate the pathogenesis of insulin resistance as the first rodent model.
Weight of ob/ob mice increases rapidly starting at 2 weeks of age, and can
reach up to three fold the weight of wild-type controls (Yamaguchi, 2014).
By 3 weeks to a month of age, hyperphagia, insulin resistance and
hyperinsulinemia are apparent, with obesity evident by 4 weeks (Coleman,
1978; King and Bowe, 2016). Even after obvious hyperglycemia detected
at 4 weeks, blood glucose levels continue to increase until reaching a peak
at 3–5 months of age with glucose levels reaching up to 400 mg/dl
(Lindström, 2007). Although there are some abnormalities in insulin
release, islets maintain insulin secretion, and the lack of complete β-cell
failure in this model means diabetes is not particular severe and indeed not
completely representative of human T2DM (King, 2012).
db/db mice: The diabetes db gene mutation occurred spontaneously in the

leptin-receptor-deficient C57BL/KsJ strain of mice and is originally
derived from autosomal recessive mutation on chromosome 4 with
complete penetrance, originating from Bar Harbor (Coleman, 1978; Wang
et al., 2013). The db/db mice were identified initially in 1966 in Jackson
Labs and is due to an autosomal recessive mutation in the leptin receptor
(Sharma et al., 2003). They can be considered as having a natural history
that closely parallels that of humans. It appears that the obesity
predisposes these mice to diabetes, and this evidence is incredibly
valuable when assessing the effect of obesity on the development of
diabetes (Cefalu, 2006; King, 2012). It becomes hyperphagic,
hyperinsulinemic, and insulin resistant early in life (within 2 weeks of
age), then develops obesity at the age of 3 to 4 weeks. The hyperglycemia
becomes manifest at the age of 4 to 8 weeks due to beta cell failure
(Fajardo et al., 2014).
Zucker Diabetic Fatty Rats: Zucker diabetic fatty (ZDF) rats were
discovered in 1961 after a cross of Merck M-strain and Sherman rats (Al-
Awar et al., 2016). The homozygous mutation (fa/fa) of the leptin
hormone receptor results in the development of type 2 diabetes in male
rats when they are fed a high-energy rodent diet. The rats induces
hyperphagia, and become obese at around 4 weeks of age (Srinivasan and
Ramarao, 2007). In addition, rats develop advanced insulin resistance and
glucose intolerance between 3 and 8 weeks of age and turn overtly
diabetic between 8 and 10 weeks of age with glucose levels in the feeding
state typically 500 mg/dl by 10-11 weeks of age (Al-Awar et al., 2016;
King and Bowe, 2016). The symptoms of this genetic obesity share many
similarities with those in obese patients with insulin-resistance or T2DM
including hyperinsulinaemic, hyperlipidaemic, hypertensive, and impaired
glucose tolerance. Therefore, the obese Zucker rat has been widely used as
a genetic model of obesity and insulin resistance (King, 2012).
Polygenic Models
KK and KK-Ay mice: The KK mice originating from Japan is a polygenic
model of obesity and T2DM (Wang et al., 2013). They exhibit mild
insulin resistance and obesity, which is more severe in male mice than in
female mice (Kitada et al., 2016). Hyperphagia, hyperinsulinaemia and
insulin resistance are main features of the KK mouse, which becomes
gradually obese from the age of 2 months to the age of 4-5 months
(Chatzigeorgiou et al., 2009). In these animals, insulin resistance precedes
the onset of obesity. The increase in insulin content is associated with
increase in number and size of pancreatic islets, but histologically
degranulation of β-cells and hypertrophy of islets are found (King, 2012;
Srinivasan and Ramarao, 2007). The KK-Ay mouse was developed by
Nishimura et al in 1969 by transferring the yellow obese gene (Ay allele)
into the KK mouse (Nishimura, 1969). KK-Ay mice are more severely
obese and are more likely to develop hyperglycemia and albuminuria at 16
weeks of age than KK mice of the same age (Kitada et al., 2016).
Therefore, these mice are widely used as an experimental model of type 2
diabetes.

New Zealand Obese Mice: The New Zealand Obese (NZO) mouse is one
of the most thoroughly investigated polygenic models for the human
metabolic syndrome and type 2 diabetes. It presents the main
characteristics of the disease complex, including early-onset obesity,
insulin resistance, dyslipidemia, and hypertension (Dunford, 2016). As a
consequence of the syndrome, male NZO mice develop type 2 like
diabetes characterized by marked hyperglycaemia and hyperinsulinemia at
earlier age (8–12 weeks), and later on by low serum insulin levels
associated with beta-cell destruction (Gitanjali et al., 2016). Additionally,
NZO mice exhibit decreased exercise activity when compared to control
or even ob/ob mice. Obesity in NZO mice is caused by a combination of
hyperphagia, insufficient physical activity, and reduced energy
expenditure with a reduction in body temperature (King and Bowe, 2016).
TALLyHO/Jng(TH) mice: The TallyHo mice are developed from an

outbred colony of Theiler original mice by selective breeding of mice that
spontaneously developed hyperglycaemia and hyperinsulinaemia (Denvir
et al., 2016). Hence, it is a model of obesity and type 2 diabetes.
Hyperglycaemia is limited to male mice, which develops at an early age,
between 10 and 14 weeks (Sah et al., 2016). Furthermore, TH mice also
exhibit increased islet insulin secretion in response to glucose and β-cell
mass. It has been used in the development of therapeutic agents for obesity
and type 2 diabetes and served as a model system for decreased exercise
capacity, impaired wound healing, periodontitis, tissue susceptibility to
hypoxia, bone loss, circadian disruption, and vasculature abnormalities
(Denvir et al., 2016).
Otsuka Long Evans Tokushima Fatty Rat: Otsuka Long Evans

Tokushima Fatty (OLETF) rats are an outbred strain of rats developed by
Drs. Long and Evans in 1915 by crossing several Wistar white females
with wild gray male rats (Cheung et al., 2009). Long Evans rats are white
with a black hood, or occasionally white with a brown hood (Kawano et
al., 1992). The spontaneously hypertensive rat exhibits essential
hypertension, hyperinsulinemia, glucose intolerance, hypertriglyceridemia
and obesity collectively representing human insulin resistance syndrome
(Sah et al., 2016). These polygenic rats develop diabetes later in life at
around 18-25 weeks old and inherited mostly in males (Abdul Rasheed et
al., 2016).
Non Obese Models

Not all type 2 diabetes patients are obese, and thus, it is important that lean
animal models of type 2 diabetes are also studied (Nagai et al., 2012).
Spontaneous models are well known in this category, e.g., Goto-Kakizaki
(GK) rats, Spontaneously Diabetic Torii (SDT) rats, Cohen diabetic rats,
and Wistar Bonn/Kobori (WBN/Kob). Chemically-induced diabetes
models such as neonatal streptozotocin-induced (Nstz) diabetic rats are
also used (Yukihito et al., 2012).
Goto-Kakizaki Rats: Goto-Kakizaki (GK) rats are a non-obese substrain

of Wistar origin that develops type 2 diabetes as a result of impaired beta
cell mass function and glucotoxicity stemming from polygenic
inheritance. They were selected through a group of eight generation-
inbreeding Wistar rats displaying high glucose levels during a glucose
tolerance test (Shafrir and Ziv, 2009). This leads to the development of a
lean model of type 2 diabetes, which is characterized by glucose
intolerance and defective glucose-induced insulin secretion caused by β
cell dysfunction and/or reduced β cell mass (Mukai et al., 2014). Thus,
adult GK rats show finally a 60% decrease in their total pancreatic β-cell
mass. However, blood glucose is elevated only after the 3-4 first weeks of
animal’s age and generally, during its lifetime, fasting glucose remains
mild and stable and rises only after challenge with glucose. GK rat is a
very useful model for studying the mechanisms of diabetes complications,

although the very early β-cell destruction remains a limitation for

depicting T2DM (Chatzigeorgiou et al., 2009).
Torii (SDT) rat: The Spontaneously Diabetic Torii (SDT) rat is a new
inbred strain of Sprague-Dawley (SD) rat established as a non-obese
model of type 2 diabetes mellitus and characterized by long survival
without insulin treatment (Srinivasan and Ramarao, 2007). The cumulative
incidence of diabetes was 100% by 32 weeks in male SDT rats, while it
was only 33% in females even at 15 months (Yukihito et al., 2012). A
clear gender difference is observed in the onset of diabetes in SDT rats.
Male SDT rats showed high plasma glucose levels (over 700 mg/dl) by 20
weeks which will lead to develop severe ocular complications such as
cataracts, retinal neovascularizations, and retinal detachment with fibrous
proliferation as well as renal abnormalities such as renal tubular dilation
and increased mesangial matrix in glomeruli (Mukai et al., 2014;
Shinohara et al., 2000). Therefore, SDT rats are a useful animal model for
investigating diabetic complications.
Cohen diabetic rat: Cohen diabetic rat, an exceptional genetical model

derived from diet-induced T2DM model by placing the rat on a synthetic
72% sucrose-copper-poor diet for 2 months, displays many features of the
human T2DM (Wang et al., 2013).The diabetes is due to β-cell
dysfunction and reduced insulin secretion (Shafrir and Ziv, 2009). The
main complications of Cohen rats were nephropathy with mesangial
expansion and thickening of the glomerular basement membrane,
proliferative retinopathy, testicular atrophy and gastrointestinal disorders,
skeletal pathology, and embryopathy (Katsuda et al., 2014).
Wistar Bonn / Kobori (WBN/Kob) rat: These animals of Wistar strain

demonstrate impaired glucose tolerance and glucosuria at 21 weeks of age
and this is seen only in males. Reduction in the number and size of islets
after 12 weeks of age was observed (Sharma et al., 2016).
Histopathological examination of the pancreas revealed fibrotic changes as
early as 3 months of age. With advancing age, the fibrosis invades the
islets, resulting in the clinical diabetic syndrome (De Angelis et al., 2009).
Diet/nutrition T2DM rodent models

Diet or nutritiontype 2 diabetic rodent models also called experimentally
or non-spontaneously induced models are not diabetic under normal
conditions (Islam and Loots, 2009). In T2DM research, genetic models
provide a better pathogenesis for the disease and a wide variety of such
models exist to study various areas of diabetic pathology, but
unfortunately, those models are very expensive, difficult to maintain and
rare amongst researchers particularly in the developing countries (Islam
and Loots, 2009). Non-genetic models, on the other hand, are far more
cost-effective, widely available and easy to develop diabetes with minimal
research facilities (Wilson and Islam, 2012). However, the available
rodent models present one or both of the two major pathogenic features of
T2DM—these being insulin resistance and, subsequently, the development
of pancreatic beta cell dysfunction (Islam and Wilson, 2012). In these
models, rats or mice develop diabetes associated with obesity as a result of
over nutrition, which mimic the metabolic syndrome in humans, and most
require long period of dietary treatment (Kiasalari et al., 2017). Sand rat,
Tuco-Tuco and Spiny mice are some models of diet/nutrition induced
obesity and type 2 diabetes.
Sand rat: Sand rat (Psammomysobesus) is a model of nutritionally

induced type 2 diabetes. The progression of diabetes in Psammomys
resembles in many respects the development of insulin resistance and
diabetes in certain human populations (Shafrir et al., 2007).The animals
develop diabetic symptoms when fed chow instead of their natural diet. In
2-3 months, the diabetic syndrome in the sand rat usually develops.
Severely hyperglycemic animals die prematurely from ketosis (Kumar et
al., 2012).
Tuco-Tuco: The diabetic syndrome in Tuco-tuco mice (Ctenomis talarum)

is similar to that in sand rats and spiny mice. They tend to have less
hyperglycemia and are less prone to ketosis. Many animals, mainly males,
become hyperphagic. In few animals degranulation of β cell is the usual
lesion in the pancreas, but amyloid hyalinization of islets has been
observed (Sharma et al., 2016).

Spiny mice: The spiny mouse (Acomyscahirinus) is found in the semi-

desert areas of the Eastern Mediterraneann. Diabetes occurs in about 15%
of the animals under laboratory conditions (Kumar et al., 2012). Some
animals show obesity, mild hyperglycemia, and hyperinsulinemia and
some have frank hyperglycemia with glucosuria that leads to fatal ketosis.
All spiny mice characteristically have massive hyperplasia of pancreatic
islets and increased pancreatic insulin content (Sharma et al., 2016).
Chemically induced T2DM rodent models

Gold thioglucose (GTG) treated obese mice: Gold thioglucose is
diabetogenic compound, which is induced hyperphagia and severe obesity
induced T2DM (Kumar et al., 2012). They produces obesity-induced
diabetes in genetically normal mouse strains. In addition, Gold thioglucose
treated DBA/2 (Dilute Brown Non- Agouti), C57BLKs, and BDF1 mice
gained weight rapidly and significantly increase non fasting plasma
glucose level within 8-12 weeks (Tripathi and Verma, 2014). These mice
showed impaired insulin secretion, mainly in early phase after glucose
load and reduced insulin content in pancreatic islets (Miyawaki et al.,
1999).
Adult Streptozotocin/ Alloxan Models: Alloxan is a uric acid derivative

that selectively destroys pancreatic β-cells by oxidative stress
mechanisms. However, the use of alloxan nowadays is significantly lower
compared to Streptozotocin (STZ) due to its lesser efficacy and some
proven side effects in animals e.g., liver and kidney damage. The STZ, on
the other hand, is a natural antibiotic produced by the bacterial species
Streptomyces achromogenes (Islam and Wilson, 2012). It is, however,
known that single high dose STZ injection (>60 mg/kg BW) results in
massive pancreatic β-cell destruction, more characteristic of T1DM,
whereas intermediate dosages of STZ injections (between 40 and 55
mg/kg BW) cause only partial impairment to insulin secretory
mechanisms seen in T2DM. A single dose lower than 35 mg/kg bw in rats
fed a normal commercial diet usually fails to elicit any hyperglycemic
effect (Srinivasan et al., 2005). These models are usually characterized by
fasting or non-fasting hyperglycemia, lowered serum insulin levels with
hyperlipidemia; however, insulin resistance is often absent in these
models. Although these models cannot be considered as appropriate

models for T2DM, they can be used for the screening of
antihyperglycemic or insulinotropic drugs and natural medicines (Islam
and Wilson, 2012).
Neonatal Streptozotocin/Alloxan Models: Rats with diabetes induced by

injection of streptozotocin/Alloxan on the day of birth, or soon thereafter,
are used to study the long-term consequences of reduced β-cell mass that
resemble those seen in human type 2 diabetes (Shafrir et al., 2006). In this
model, a peak of hyperglycaemia is seen 2 days after STZ administration
(100 mg/kg, i.v. or i.p.), which is followed by regeneration of beta cells
and normoglycaemia by day 10. However, hyperglycaemia returns by 6
weeks, which is thought to be due to inadequate beta cells mass and beta
cell dysfunction. Therefore, in the later phase, this model can be used to
study type 2 diabetes (King, 2012). Single injection of STZ at the dose
range of 80-100 mg /kg of STZ (iv or ip or sc) to one or two or five day
old Wistar or Sprague-Dawley neonatal rats has been reported to produce
type 2 diabetic conditions (Srinivasan and Ramarao, 2007). Some
investigators have also developed neonatal type 2 diabetic models by
injecting ALX (200 mg/kg, ip) to male neonatal rats at age of 2, 4 or 6 day
after birth and found to be much useful for the investigation of long term
complication of type 2 diabetes (Kodama et al., 1993). In these models,
diabetes was characterized by mild to moderate hyperglycemia, increased
blood glycated hemoglobin, urinary glucose excretion, and increased food
intake (Islam and Wilson, 2012). However, this model takes quite a long
time (at least 12 weeks) to induce diabetes which may not be suitable for
quick and routine pharmacological screening of anti-type 2 diabetic drugs
or natural medicines. Furthermore, many of these models have not been
validated by anti-diabetic drugs and thus limit their suitability as an
appropriate model for T2DM (Islam and Loots, 2009).
Nicotinamide–Streptozotocin Models: Administration of both

streptozotocin (STZ) and nicotinamide (NA) has been proposed to induce
T2DM in rats. STZ is well known to cause pancreatic β-cell damage,
whereas NA is administered to rats to partially protect insulin secreting
cells against STZ (Lenzen, 2008). The effects induced in rats by STZ and

NA vary depending on the doses of these two compounds, the age of the
animals and the time of NA administration in relation to the administration
of STZ. Other factors, such as the administration route of STZ and the
nutritional state of rats, may also have certain influence (Domingo et al.,
1995). In the case of relatively low doses of NA given to rats, its
protective action is negligible. Conversely, high doses of NA may provide
full protection (Tubiana and Aurengo, 2006). The age of rats is vital, since
β-cells of younger animals are less sensitive to STZ and are better
protected by NA. It is also known that the protective action of NA on β-
cells decreases with the time elapsed after administration of STZ to rats.
In the majority of experiments, NA is given to rats 15 minutes before STZ
injection (Szkudelski, 2012).
Combinations of chemicals and diet T2DM models

The most commonly used non-genetic rodent models of diabetes are those
induced by streptozotocin or alloxan, in addition to diet (Lenzen, 2008).
Diet composition has been considered an important factor in the
impairment of insulin activity (Dourmashkin et al., 2005). Various studies
(Bansal et al., 2012; Veerapur et al., 2012; Zhang et al., 2009) showed that
the administration of a high-fat diet (HFD) to rats for 2 months or lower is
a fast and easy way to induce metabolic syndrome, associated with
metabolic and oxidative disorders, without modulation of glycaemia
(Auberval et al., 2014). However, diet rich in fat as well as sugar is a
greater risk factor for these disorders than a diet that is rich in either fats or
sugars (Lozano et al., 2016). Moreover, these models require lengthy
feeding regimens before any decline in β-cell mass is detectable. To
overcome this barrier, a low dose of streptozotocin or alloxan have been
described in the rat or mice to deplete β-cell mass chemically after
induction of diet-induced insulin resistance (Podell et al., 2017).
Fat fed/STZ diabetic rodents, developed by combination of diet-induced

insulin resistance and relatively low-dose streptozotocin (35–50 mg/kg)
provide a novel animal model for diet induced T2DM (Srinivasan and
Ramarao, 2007). In these animals, insulin resistance is generated by
feeding the animals with high fat diet (HFD). Subsequently,
hyperglycemia is induced by injection with a low dose of STZ that does
not cause diabetes in standard diet fed animals (Furman, 2015). Thus,
these fat-fed/STZ-treated animals simulate natural disease progression and
metabolic characteristics typical of individuals at an increased risk of
developing T2DM because of insulin resistance and obesity (Reuter,
2007). Suitable animal strains for high fat/STZ models are C57BL/6J mice
as well as rats, preferably male Sprague-Dawley rats. Diets from 40% to
60% calories as fat have been used together with STZ injections of 35–50
mg/kg. Induction times vary from 2 to 4 weeks up to several weeks,
depending to type of diet and dose of STZ (Reed et al., 2000; Reuter,
2007; Srinivasan et al., 2005). The high fat fed low dose STZ models have
several advantages, including cost-effective, developed in short time and
are suitable for in vivo evaluation of anti-diabetic agents (Srinivasan and
Ramarao, 2007).
Similar to HFD, the induction of insulin resistance through fructose-

feeding in animals has been employed previously (Hininger et al., 2009).
Fructose could be supplied adlibitum, either in drinking water (20%) or
with diets (60%of the total energy) for a short or longer period to induce
insulin resistance or T2DM, respectively, in experimental animals (Dai et
al., 1994). Hence, the combination of fructose-feeding for a shorter period
of time (less than 2 months) and a lower dose of STZ injection (35–50
mg/kg) may induce all major pathogeneses of T2D in rats (Patel et al.,
2009).
Surgically induced T2DM rodent models

Partial Pancreatectomized Models: As a means to avoid liver and kidney
damage induced by alloxan, researchers developed a new method to
induce T2DM in animals through partial pancreatectomy (Islam and
Wilson, 2012). Partial pancreatectomy in animals performed as 70 or 90
per cent (usually 90%) dissection of pancreas has been reported in various
animal species mostly in dogs, pigs, rabbit and also rats. It does not cause
severe form of diabetes and is characterized by moderate hyperglycaemia
with neither reduction in body weight nor reduction in plasma insulin
levels (Srinivasan and Ramarao, 2007). However, better degree of
glycaemia or stable form of diabetes for long duration can be achieved by
the combination of partial pancreatectomy with ALX/STZ injection. This

model was accomplished by 50% pancreatectomy in combination of a 350

mg/kg BW nicotinamide injection prior to and after intraperitoneal
injection of 200 mg/kg BW STZ in BALB/c mice (Islam and Wilson,
2012).
Ventromedial hypothalamus (VMH) diabetic rats: VMH dietary obese

diabetic rat has been developed by experimental surgical manipulation of
genetically normal animals without the reduction in pancreatic beta cell
mass, resembling type-2 diabetes, by combining bilateral electrolyte lesion
of VMH and feeding the high fat and high sucrose diet to the animal
(Singh and Pathak, 2015). It is characterized by obvious obesity,
hyperinsulinaemia, hypertriglyceridaemia, insulin resistance, impaired
glucose tolerance, moderate to severe fasting hyperglycaemia and
defective regulation of insulin secretory response despite extremely high
insulin secretory capacity. It is interesting that significant hyperphagia is
observed despite increased leptin levels (leptin resistance) in the VMH
lesioned rats (Srinivasan and Ramarao, 2007).
Transgenic/knock-out T2DM Models

These transgenic animals are usually helpful in getting insights to gene
regulation and development, pathogenesis, treatment of disease and
finding new targets for that (Ranjan and Sharma, 2015). Generally,
transgenic animals, especially mice, are made by transferring and altering
the site or expression level of functional gene (transgene) or by deleting
specific endogenous genes (knockout) or by placing them under the
control of alternate promoter regions (Margawati, 2003). These models are
developed in order to explore the role of associated genes and their effects
on peripheral insulin action such as insulin receptor, IRS-1, IRS-2, GLUT
4, PPAR-γ and TNF-α as well as in insulin secretion such as GLUT-2,
GK, IAPP and GLP-1 and also in hepatic glucose production (PEPCK
expression) associated with T2DM development (Ranjan and Sharma,
2015; Sharma et al., 2016). Although significant advances in this field
have arisen in recent years, especially with the advent of transgenic mice,
there have been a few studies carried out involving natural products on
these models.
Conclusion:
The animal models of T2DM are very useful means for studying the
pathophysiology and the clinical phases of the disease. Actually, they are
always used as the initial step for examining a new therapy. Each model
provides unique advantages specific for an area of T2DM study or its
complications. An ideal model should typically mimic the natural disease
pattern as closely as possible with the two major pathogeneses, insulin
resistance, and partial pancreatic beta cell dysfunction. Therefore, the
continuing research for inventing new models has always positive critics
and animal models will continue to have a major and meaningful place in
diabetes research. However, every researcher should only utilize animals
only when they are indispensable for a study and avoid causing them pain,
distress, suffering and lasting harm.

References
Abdul Rasheed, V., Surenrda, K., Afeefa, C., and Rajesh, V. (2016). A
comprehensive review on in vitro and in vivo models used for
hepatoprotective Activity. Journal of Pharmaceutical Sciences and
Research 8, 184-189.
Al-Awar, A., Kupai, K., Veszelka, M., Szűcs, G., Attieh, Z., Murlasits, Z.,
Török, S., Pósa, A., and Varga, C. (2016). Experimental diabetes
mellitus in different animal models. Journal of Diabetes Research
2016.
Andersen, M. L., and Tufik, S. (2015). "Rodent Model as Tools in Ethical
Biomedical Research," Springer.
Angelis, M. H., Nicholson, G., Selloum, M., White, J. K., Morgan, H.,
Ramirez-Solis, R., Sorg, T., Wells, S., Fuchs, H., and Fray, M.
(2015). Analysis of mammalian gene function through broad-based
phenotypic screens across a consortium of mouse clinics. Nature
genetics 47, 969-978.
Auberval, N., Dal, S., Bietiger, W., Pinget, M., Jeandidier, N., Maillard-
Pedracini, E., Schini-Kerth, V., and Sigrist, S. (2014). Metabolic
and oxidative stress markers in Wistar rats after 2 months on a
high-fat diet. Diabetology & metabolic syndrome 6, 130.
Balcombe, J. P. (2006). Laboratory environments and rodents' behavioural
needs: a review. Laboratory animals 40, 217-235.
Bansal, P., Paul, P., Mudgal, J., Nayak, P. G., Pannakal, S. T.,
Priyadarsini, K., and Unnikrishnan, M. (2012). Antidiabetic,
antihyperlipidemic and antioxidant effects of the flavonoid rich
fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-
induced diabetes in mice. Experimental and Toxicologic Pathology
64, 651-658.
Cefalu, W. T. (2006). Animal models of type 2 diabetes: clinical

presentation and pathophysiological relevance to the human
condition. ILAR journal 47, 186-198.
Chatzigeorgiou, A., Halapas, A., Kalafatakis, K., and Kamper, E. (2009).
The use of animal models in the study of diabetes mellitus. In Vivo
23, 245-258.
Cheung, G. W., Kokorovic, A., Lam, C. K., Chari, M., and Lam, T. K.
(2009). Intestinal cholecystokinin controls glucose production
through a neuronal network. Cell metabolism 10, 99-109.
Coleman, D. (1978). Obese and diabetes: two mutant genes causing
diabetes-obesity syndromes in mice. Diabetologia 14, 141-148.
Dai, S., Todd, M. E., Lee, S., and McNeill, J. H. (1994). Fructose loading
induces cardiovascular and metabolic changes in nondiabetic and
diabetic rats. Canadian journal of physiology and pharmacology
72, 771-781.
De Angelis, K., Irigoyen, M. C., and Morris, M. (2009). Diabetes and
cardiovascular autonomic dysfunction: application of animal
models. Autonomic Neuroscience 145, 3-10.
Denvir, J., Boskovic, G., Fan, J., Primerano, D. A., Parkman, J. K., and
Kim, J. H. (2016). Whole genome sequence analysis of the
TALLYHO/Jng mouse. BMC genomics 17, 907.
Domingo, J. L., Gomez, M., Sanchez, D. J., Llobet, J. M., and Keen, C. L.
(1995). Toxicology of vanadium compounds in diabetic rats: the
action of chelating agents on vanadium accumulation. Molecular
and cellular biochemistry 153, 233-240.

Dourmashkin, J., Chang, G., Gayles, E., Hill, J., Fried, S., Julien, C., and
Leibowitz, S. (2005). Different forms of obesity as a function of
diet composition. International journal of obesity 29, 1368-1378.
Dunford, E. (2016). The Relationship Between Elevations in
Glucocorticoids and Diabetes Development in Rats on Skeletal
Muscle Insulin Resistance and the Microvasculature, PhD. Thesis,
York University, Canada.
Fajans, S., Bell, G., and Polonsky, K. (2001). Molecular mechanisms and
clinical pathophysiology of maturity-onset diabetes of the young.
New England Journal of Medicine 345, 971-980.
Fajardo, R. J., Karim, L., Calley, V. I., and Bouxsein, M. L. (2014). A
review of rodent models of type 2 diabetic skeletal fragility.
Journal of Bone and Mineral Research 29, 1025-1040.
Furman, B. L. (2015). Streptozotocin‐induced diabetic models in mice and
rats. Current Protocols in Pharmacology, 5.47. 1-5.47. 20.
Gitanjali, M., Prasanna, K. P., and Trilochan, S. (2016). Animal models
for type 2 diabetes: A review. World Journal of Pharmaceutical
Sciences 1, 140-147.
Hattersley, A. (1998). Maturity‐onset diabetes of the young: clinical
heterogeneity explained by genetic heterogeneity. Diabetic
Medicine 15, 15-24.
Hattersley, A. (2005). Molecular genetics goes to the diabetes clinic.
Clinical medicine 5, 476-481.
Hininger, F., Benaraba, R., Coves, S., Anderson, R., and Roussel, A.
(2009). Green tea extract decreases oxidative stress and improves
insulin sensitivity in an animal model of insulin resistance, the
fructose-fed rat. Journal of the American College of Nutrition 28,

355-361.
Islam, M., and Loots, T. (2009). Experimental rodent models of type 2
diabetes: a review. Methods and Findings in Experimental and
Clinical Pharmacology 31, 249-261.
Islam, M. S., and Wilson, R. D. (2012). Experimentally induced rodent
models of type 2 diabetes. Methods in Molecular Biology 933,
161-174
Kanasaki, K., and Koya, D. (2011). Biology of obesity: lessons from
animal models of obesity. BioMed Research International 2011.
Katsuda, Y., Ohta, T., Miyajima, K., Kemmochi, Y., Sasase, T., Tong, B.,
Shinohara, M., and Yamada, T. (2014). Diabetic complications in
obese type 2 diabetic rat models. Experimental Animals 63, 121-
132.
Kawano, K., Hirashima, T., Mori, S., Saitoh, Y., Kurosumi, M., and
Natori, T. (1992). Spontaneous long-term hyperglycemic rat with
diabetic complications: Otsuka Long-Evans Tokushima Fatty
(OLETF) strain. Diabetes 41, 1422-1428.
Kiasalari, Z., Rahmani, T., Mahmoudi, N., Baluchnejadmojarad, T., and
Roghani, M. (2017). Diosgenin ameliorates development of
neuropathic pain in diabetic rats: Involvement of oxidative stress
and inflammation. Biomedicine & Pharmacotherapy 86, 654-661.
King, A., and Bowe, J. (2016). Animal models for diabetes:
Understanding the pathogenesis and finding new treatments.
Biochemical pharmacology 99, 1-10.
King, A. J. (2012). The use of animal models in diabetes research. British
journal of pharmacology 166, 877-894.

Kitada, M., Ogura, Y., and Koya, D. (2016). Rodent models of diabetic
nephropathy: their utility and limitations. International Journal of
Nephrology and Renovascular Disease 9, 279
Klupa, T., Skupien, J., and Malecki, M. (2012). Monogenic Models: What
Have the Single Gene Disorders Taught Us? Current Diabetes
Reports 12, 659-666.
Kodama, T., Iwase, M., Nunoi, K., Maki, Y., Yoshinari, M., and
Fujishima, M. (1993). A new diabetes model induced by neonatal
alloxan treatment in rats. Diabetes Research and Clinical Practice
20, 183-189
Kumar, S., Singh, R., Vasudeva, N., and Sharma, S. (2012). Acute and
chronic animal models for the evaluation of anti-diabetic agents.
Cardiovascular diabetology 11, 9.
Leiter, E. H. (2009). Selecting the “right” mouse model for metabolic
syndrome and type 2 diabetes research. Methods in Molecular
Biology 560, 1-17.
Lenzen, S. (2008). The mechanisms of alloxan-and streptozotocin-induced
diabetes. Diabetologia 51, 216-226.
Lindström, P. (2007). The physiology of obese-hyperglycemic mice
[ob/ob mice]. The scientific world journal 7, 666-685.
Lozano, I., Van der Werf, R., Bietiger, W., Seyfritz, E., Peronet, C.,
Pinget, M., Jeandidier, N., Maillard, E., Marchioni, E., and Sigrist,
S. (2016). High-fructose and high-fat diet-induced disorders in
rats: impact on diabetes risk, hepatic and vascular complications.
Nutrition & metabolism 13, 15.
Malecki, M. T., Mlynarski, W., and Skupien, J. (2008). Can geneticists

help clinicians to understand and treat non-autoimmune diabetes?
diabetes research and clinical practice 82, S83-S93.
Margawati, E. T. (2003). Transgenic animals: their benefits to human
welfare. American Institute for Biological Sciences.
McCarthy, M. I., and Hattersley, A. T. (2001). Molecular diagnostics in
monogenic and multifactorial forms of type 2 diabetes. Expert
review of molecular diagnostics 1, 403-412.
Miyawaki, K., Yamada, Y., Yano, H., Niwa, H., Ban, N., Ihara, Y.,
Kubota, A., Fujimoto, S., Kajikawa, M., and Kuroe, A. (1999).
Glucose intolerance caused by a defect in the entero-insular axis: a
study in gastric inhibitory polypeptide receptor knockout mice.
Proceedings of the National Academy of Sciences 96, 14843-
14847.
Mukai, E., Ohta, T., Kawamura, H., Lee, E.-Y., Morita, A., Sasase, T.,
Miyajima, K., Inagaki, N., Iwanaga, T., and Miki, T. (2014).
Enhanced vascular endothelial growth factor signaling in islets
contributes to β cell injury and consequential diabetes in
spontaneously diabetic Torii rats. Diabetes research and clinical
practice 106, 303-311.
Nagai, K., Fukushima, T., Oike, H., and Kobori, M. (2012). High glucose
increases the expression of proinflammatory cytokines and
secretion of TNFα and β-hexosaminidase in human mast cells.
European journal of pharmacology 687, 39-45.
Nishimura, M. (1969). Breeding of mice strains for diabetes mellitus. Exp
Anim 18, 147-157.

Oakes, N. D., Thalén, P., Hultstrand, T., Jacinto, S., Camejo, G., Wallin,
B., and Ljung, B. (2005). Tesaglitazar, a dual PPARα/γ agonist,
ameliorates glucose and lipid intolerance in obese Zucker rats.
American Journal of Physiology-Regulatory, Integrative and
Comparative Physiology 289, R938-R946.
Patel, J., Iyer, A., and Brown, L. (2009). Evaluation of the chronic
complications of diabetes in a high fructose diet in rats.
Podell, B. K., Ackart, D. F., Richardson, M. A., DiLisio, J. E., Pulford, B.,
and Basaraba, R. J. (2017). A model of type 2 diabetes in the
guinea pig using sequential diet-induced glucose intolerance and
streptozotocin treatment. Disease Models & Mechanisms, dmm.
025593.
Ranjan, S., and Sharma, P. K. (2015). Experimental Model Organisms in
Type 2 Diabetes Research: A Review. International Journal 3,
344-356.
Reed, M., Meszaros, K., Entes, L., Claypool, M., Pinkett, J., Gadbois, T.,
and Reaven, G. (2000). A new rat model of type 2 diabetes: the fat-
fed, streptozotocin-treated rat. Metabolism: Clinical and
Experimental 49, 1390.
Renner, S., Dobenecker, B., Blutke, A., Zöls, S., Wanke, R., Ritzmann,
M., and Wolf, E. (2016). Comparative aspects of rodent and
nonrodent animal models for mechanistic and translational
diabetes research. Theriogenology 86, 406-421.
Reuter, T. Y. (2007). Diet-induced models for obesity and type 2 diabetes.
Drug Discovery Today: Disease Models 4, 3-8.
Sah, S. P., Singh, B., Choudhary, S., and Kumar, A. (2016). Animal
models of insulin resistance: A review. Pharmacological Reports
68, 1165-1177.
Shafrir, E., Kalman, R., and Ziv, E. (2007). Psammomys obesus. In
"Animal Models of Diabetes, Second Edition: Frontiers in
Research", pp. 289-310. CRC Press.
Shafrir, E., and Ziv, E. (2009). A useful list of spontaneously arising
animal models of obesity and diabetes. American Journal of
Physiology - Endocrinology And Metabolism 296, E1450-E1452.
Shafrir, E., Ziv, E., and Kalman, R. (2006). Nutritionally induced diabetes
in desert rodents as models of type 2 diabetes: Acomys cahirinus
(spiny mice) and Psammomys obesus (desert gerbil). ILAR Journal
47, 212-224
Sharma, K., McCue, P., and Dunn, S. R. (2003). Diabetic kidney disease
in the db/dbmouse. American Journal of Physiology-Renal
Physiology 284, F1138-F1144.
Sharma, P., Garg, A., Garg, S., and Singh, V. (2016). Animal model used
for experimental study of Diabetes Mellitus: An overview. Asian
Journal of Biomaterial Research 2, 99-110.
Shinohara, M., Masuyama, T., Shoda, T., Takahashi, T., Katsuda, Y.,
Komeda, K., Kuroki, M., Kakehashi, A., and Kanazaw, Y. (2000).
A new spontaneously diabetic non-obese Torii rat strain with
severe ocular complications. Journal of Diabetes Research 1, 89-
100.
Singh, M. P., and Pathak, K. (2015). Animal models for biological
screening of anti-diabetic drugs: An overview. European Journal
of Experimental Biology 5, 37-48.

Srinivasan, K., and Ramarao, P. (2007). Animal model in type 2 diabetes

research: An overview. Indian Journal of Medical Research 125,
451-472.
Srinivasan, K., Viswanad, B., Asrat, L., Kaul, C., and Ramarao, P. (2005).
Combination of high-fat diet-fed and low-dose streptozotocin-
treated rat: a model for type 2 diabetes and pharmacological
screening. Pharmacological Research 52, 313-320.
Szkudelski, T. (2012). Streptozotocin-nicotinamide-induced diabetes in
the rat. Characteristics of the experimental model. Experimental
Biology and Medicine 237, 481-490.
Tiwari, P. (2015). Recent trends in therapeutic approaches for diabetes
management: a comprehensive update. Journal of diabetes
research 2015.
Tripathi, V., and Verma, J. (2014). Different models used to induce
diabetes: a comprehensive review. Int J Pharm Sci 6, 29-32.
Tubiana, M., and Aurengo, A. (2006). Dose–effect relationship and
estimation of the carcinogenic effects of low doses of ionising
radiation: the Joint Report of the Académie des Sciences (Paris)
and of the Académie Nationale de Médecine. International Journal
of Low Radiation 2, 135-153
Veerapur, V., Prabhakar, K., Thippeswamy, B., Bansal, P., Srinivasan, K.,
and Unnikrishnan, M. (2012). Antidiabetic effect of Ficus
racemosa Linn. stem bark in high-fat diet and low-dose
streptozotocin-induced type 2 diabetic rats: A mechanistic study.
Food Chemistry 132, 186-193.
Wall, R., and Shani, M. (2008). Are animal models as good as we think?
Theriogenology 69, 2-9.
Wang, Y.-w., Sun, G.-d., Sun, J., Liu, S.-j., Wang, J., Xu, X.-h., and Miao,
L.-n. (2013). Spontaneous Type 2 Diabetic Rodent Models.
Journal of Diabetes Research 2013, 8.
WHO (2016). Global report on diabetes.
Wilson, R. D., and Islam, M. S. (2012). Fructose-fed streptozotocin-
injected rat: an alternative model for type 2 diabetes.
Pharmacological Reports 64, 129-139.
Yamaguchi, M. (2014). Type 1 diabetic bone loss is prevented by novel
osteogenic factors.
Yukihito, I., Takeshi, O., and, and Tomohiko, S. (2012). Non-Obese Type
2 Diabetes Animals Models, Glucose Tolerance. Glucose
Tolerance 13, 223-242.
Zhang, M., Lv, X.-Y., Li, J., Xu, Z.-G., and Chen, L. (2009). The
characterization of high-fat diet and multiple low-dose
streptozotocin induced type 2 diabetes rat model. Experimental
Diabetes Research 2008.
Zone, C., and Guide, S. (2017). Avoiding complications in type 2 diabetes.
Sign 3531.

Rodent Models of Type 2 Diabetes Mellitus

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Rodent Models of Type 2 Diabetes Mellitus

Uploaded by

Copyright:

Available Formats

Hebron University Research Journal-A (Natural Sciences) - ((‫مجلة‬

‫ أ )العلوم الطبيعيه‬-‫جامعة الخليل للبحوث‬

Volume 7 Issue 1 Article 3

Rodent Models of Type 2 Diabetes Mellitus

Follow this and additional works at: https://digitalcommons.aaru.edu.jo/hujr_a

Part of the Life Sciences Commons

Hebron University Research Journal( A) H.U.R.J. is available online at

Rodent Models of Type 2 Diabetes Mellitus

Dr. Zaki Ali Tubesha

Keywords: Animal models, Diabetes, Rodents, Obesity

Published by Arab Journals Platform, 2017 1

In addition, medications used for the treatment of T2DM are associated

Spontaneous (genetic) T2DM rodent models

Published by Arab Journals Platform, 2017 3

insulin secretion or from an abnormal response to insulin (Klupa et al.,

ob/ob mice: The ob/obmice strain, from the Bar Harbor-Jackson

db/db mice: The diabetes db gene mutation occurred spontaneously in the

Published by Arab Journals Platform, 2017 5

TALLyHO/Jng(TH) mice: The TallyHo mice are developed from an

Otsuka Long Evans Tokushima Fatty Rat: Otsuka Long Evans

Non Obese Models

Goto-Kakizaki Rats: Goto-Kakizaki (GK) rats are a non-obese substrain

Published by Arab Journals Platform, 2017 7

although the very early β-cell destruction remains a limitation for

Cohen diabetic rat: Cohen diabetic rat, an exceptional genetical model

Wistar Bonn / Kobori (WBN/Kob) rat: These animals of Wistar strain

Diet/nutrition T2DM rodent models

Sand rat: Sand rat (Psammomysobesus) is a model of nutritionally

Tuco-Tuco: The diabetic syndrome in Tuco-tuco mice (Ctenomis talarum)

Published by Arab Journals Platform, 2017 9

Spiny mice: The spiny mouse (Acomyscahirinus) is found in the semi-

Chemically induced T2DM rodent models

Adult Streptozotocin/ Alloxan Models: Alloxan is a uric acid derivative

models. Although these models cannot be considered as appropriate

Neonatal Streptozotocin/Alloxan Models: Rats with diabetes induced by

Nicotinamide–Streptozotocin Models: Administration of both

Published by Arab Journals Platform, 2017 11

Combinations of chemicals and diet T2DM models

Fat fed/STZ diabetic rodents, developed by combination of diet-induced

Similar to HFD, the induction of insulin resistance through fructose-

Surgically induced T2DM rodent models

Published by Arab Journals Platform, 2017 13

model was accomplished by 50% pancreatectomy in combination of a 350

Ventromedial hypothalamus (VMH) diabetic rats: VMH dietary obese

Transgenic/knock-out T2DM Models

Published by Arab Journals Platform, 2017 15

Cefalu, W. T. (2006). Animal models of type 2 diabetes: clinical

Published by Arab Journals Platform, 2017 17

fructose-fed rat. Journal of the American College of Nutrition 28,

Published by Arab Journals Platform, 2017 19

Malecki, M. T., Mlynarski, W., and Skupien, J. (2008). Can geneticists

Published by Arab Journals Platform, 2017 21

Published by Arab Journals Platform, 2017 23

Srinivasan, K., and Ramarao, P. (2007). Animal model in type 2 diabetes

Published by Arab Journals Platform, 2017 25

You might also like